Do Your Gut Microbes Determine How Well Immunotherapy Works for Lung Cancer?

Our bodies are teeming with microorganisms, in fact only 10% of the 100 trillion cells in us are human (yes, the rest are microbes!). The other 90 trillion cells or so are microorganisms, and the vast majority are either beneficial or neutral microbes. Only a small number are potentially bad guys. Most of these microorganisms are found in our gastrointestinal tract, extending from our lips down to our anus, with, by far, the highest concentrations found in our large intestine (gut).

The majority of these microbes (3-5 pounds worth) are beneficial to our health and are heavily involved in numerous highly important activities such as helping us absorb nutrients, controlling harmful microorganisms, and especially keeping our immune system strong. In fact, we would not be healthy nor could we live very long without these vitally important microbial tenants inhabiting our intestinal "apartment house." Collectively we refer to all microorganisms in the intestines as the "gut microbiome."

Based on results from numerous mice studies, two different melanoma trials conducted at other centers investigated the relationship between immunotherapy outcomes and the gut bacteria. The investigators obtained gut bacteria from fecal samples before the patients underwent immunotherapy for melanoma. In these observational studies recently presented (ASCO 2017), they found that the actual composition of the gut bacteria made a difference in how well the patients responded to immunotherapy.

Dr. Christine Pierce (Department of Epidemiology) and Dr. Lary Robinson (Department of Thoracic Oncology) believe that the composition of bacteria in the gut may also have a strong influence on how well advanced lung cancer patients respond to immunotherapy. Therefore they are conducting an observational clinical trial (“The Gut Microbiome and Anti-PD-1 Immunotherapy in Non-small Cell Lung Cancer”) at Moffitt Cancer Center to investigate this hypothesis in lung cancer patients undergoing immunotherapy. They hope to identify the bacterial composition that gives the clinical best response to cancer treatment.

Finding a positive correlation will not only allow us to use the gut microbiome as a biomarker to predict how well future patients may respond to treatment, but it also raises the tantalizing prospect of modifying the patient’s gut bacteria before therapy (using simple diet changes, prebiotics and probiotics), with the expectation of improved effectiveness of immunotherapy.

"Ideally, we will be able to use some (or all) of these non-toxic inexpensive interventions prospectively in a trial with patients who will be undergoing lung cancer treatment,” says Dr. Robinson. "But first we must prove a strong correlation."

This ongoing study at Moffitt about the relationship of gut bacteria and lung cancer therapy is currently only observational. No scientific attempt has yet been made to modify the gut bacteria to improve cancer treatment results. If the results of these current ongoing studies are conclusive as we think they will be, then we, and likely other scientists, will plan to begin a prospective interventional trial to modify the gut bacteria of patients prior to cancer treatment, hoping to improve cancer treatment results.

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